Phase 3 Clinical Trial: D-methionine to Reduce Noise-Induced Hearing Loss (NIHL)

NCT ID: NCT02903355

Last Updated: 2022-06-28

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 351 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-09-30
• Study Completion Date: 2017-12-31

Brief Summary

This prospective study is a randomized, double-blind, placebo-controlled Phase 3 clinical trial of oral D-methionine (D-met) to reduce noise-induced hearing loss (NIHL) and tinnitus. The goal of the study is to develop a safe, oral pharmacological agent to augment physical hearing protectors for noise exposures that exceed the protective capabilities of ear plugs and/or muffs. The study population is a cohort of Drill Sergeant (DS) instructor trainees during and 22 days after their 11 day weapons training. The primary objective of this study is to determine the efficacy of D-met in preventing NIHL or reducing tinnitus secondary to a minimum of 500 rounds of M-16 weapons training occurring over an 11 day period.

Detailed Description

Hearing loss can render a soldier less able to detect and identify the enemy, less able to understand commands, particularly in background noise typical on the battlefield, and may permanently reduce quality of life. In some cases, hearing loss may preclude redeployment or result in less optimal job assignment. Currently, no FDA approved pharmacological prevention exists for noise-induced hearing loss (NIHL). We have documented in animal studies that administration of D-methionine (D-met) can reduce or prevent NIHL. We now need to determine if it has similar efficacy in humans. Although we have not yet tested D-met on protection from noise-induced tinnitus in animals, this clinical trial would provide us the opportunity to also test for protection from noise induced tinnitus simultaneously.

Objective Hypotheses:

Primary Hypothesis: Administration of oral D-methionine prior to, during and 4 days post-weapons training will reduce or prevent permanent noise-induced hearing loss.

Secondary Hypothesis: Administration of oral D-methionine prior to, during and 4 days post-weapons training will reduce or prevent noise-induced tinnitus.

Specific Aims:

To determine whether administering oral D-met can prevent permanent NIHL after weapons training. This aim will be addressed by comparing the results of D-met versus placebo administration starting 3 days prior to, during the 11 day period of weapons training (Monday-Friday for first week, Monday-Thursday for second week), and 4 days after for a total of 18 days. Pure tone hearing thresholds will be assessed before and 22 days after completion of weapons training (ie; 18 days after the last day of study drug/placebo administration).

To determine whether administering oral D-met can prevent tinnitus after weapons training. This aim will be addressed by comparing the results of D-met versus placebo administration starting 3 days prior to, during the 11 day period of weapons training (Monday-Friday for first week, Monday-Thursday for second week), and 4 days after for a total of 18 days. Tinnitus questionnaires will be assessed before and 22 days after completion of weapons training (ie; 18 days after the last day of study drug/placebo administration).

To monitor for any potential side effects of D-met in human subjects. This aim will be accomplished by subject query on each day study drug is dispensed (twice daily) and at final study visit, routing of any adverse event reports to study medical personnel, statisticians and to the Food and Drug Administration (FDA).

Conditions

Noise-induced Hearing Loss

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

Placebo

Placebo contains sorbitol, orange flavor and purified water; is flavor and color matched to D-Met.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo contains sorbitol, orange flavor and purified water; is flavor and color matched to D-Met.

D-methionine, oral liquid suspension

D-methionine liquid suspension also contains sorbitol, orange flavor and purified water Intervention: Drug: D-methionine, oral liquid suspension.

Group Type: EXPERIMENTAL

D-methionine

Intervention Type: DRUG

D-methionine, oral liquid suspension

Interventions

D-methionine

D-methionine, oral liquid suspension

Intervention Type: DRUG

Placebo

Placebo contains sorbitol, orange flavor and purified water; is flavor and color matched to D-Met.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

Male or female 21 to 45 years of age Negative pregnancy test at enrollment and prior to taking study drug Willing to use an effective method of birth control during the study (Both male and female participants should avoid pregnancy during study) Pure tone air conduction threshold average at 0.5, 1 and 2 kHz of no greater than 40 dB HL bilaterally with no air bone gaps greater than 10 dB and normal otoscopy and tympanometry screens Willing to refrain from using supplements containing or derived from protein while participating in this study Ability to comply with all study requirements

Exclusion Criteria

History of allergic or idiosyncratic reaction to methionine, amino acid mixtures, nutritional supplements, egg white, or other proteins or food additives Vegetarian (Individual excludes meat and fish from their diet) History of chronic balance disorders Abnormal otoscopic findings, otologic surgery, autoimmune inner ear disease, significant air-bone gaps, abnormal tympanograms or other indication of middle-ear abnormality, history of fluctuant hearing or asymmetric hearing worse than 25 dB at any frequency in either ear, perilymphatic fistula, tumor of the auditory system, or other CNS disorder that is likely to affect hearing Treatment with intravenous (IV) antibiotics within the past 6 months Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of any drug Treatment for alcohol or substance abuse within past 6 months Women of childbearing age who are not using effective contraceptive methods and who may become pregnant during the course of the study Women who are pregnant or breastfeeding. National Guardsmen History of psychotic schizophrenia Exposure within the previous 6 months to systemic ototoxic substances including aminoglycosides or vancomycin Body weight exceeding 225 pounds Renal impairment measured as eGFR < 50 on screening creatinine clearance blood draw.

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Southern Illinois University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Kathleen Campbell, PhD

Role: PRINCIPAL_INVESTIGATOR

MetArmor, Inc.

CPT William Grimes, MD

Role: STUDY_DIRECTOR

United States Department of Defense, US Army Ft. Jackson, South Carolina

Locations

Moncrief Army Community Hospital

Fort Jackson, South Carolina, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

01345474

Identifier Type: -

Identifier Source: org_study_id

NCT01345474

Identifier Type: -

Identifier Source: nct_alias